Human immunodeficiency virus (HIV) is a lentivirus that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk. Within these bodily fluids. HIV is present as both free virus particles and virus within infected immune cells. The four major routes of transmission are unsafe sex, contaminated needles, breast milk, and perinatal transmission. Screening of blood products for HIV has largely eliminated transmission through blood transfusions or infected blood products in the developed world.
HIV infection in humans is considered pandemic by the World Health Organization. HIV infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells), macrophages, and dendritic cells. HIV infection leads to low levels of CD4+ T cells through three main mechanisms: direct viral killing of infected cells; increased rates of apoptosis in infected cells; and killing of infected CD4+ T cells by CD8+ cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections.
Most untreated people infected with HIV eventually develop AIDS. These individuals usually die from opportunistic infections or malignancies associated with the progressive failure of the immune system. HIV progresses to AIDS at a variable rate affected by viral, host, and environmental factors; most will progress to AIDS within 10 years of HIV infection; some will progress much sooner, and some will take much longer.
A small percentage of HIV-infected individuals retain high levels of CD4+ T-cells without anti-retroviral therapy. However, most have detectable viral load and will eventually progress to AIDS without treatment, albeit more slowly than others. These individuals are classified as HIV controllers or long-term non-progressors. Subjects who maintain CD4+ T cell counts and also have low or clinically undetectable viral load without anti-retroviral treatment are known as elite controllers.
Treatment with anti-retroviral drugs can reduce both the mortality and the morbidity of HIV infection. Although numerous medications are available to inhibit development of AIDS and slow progression of the disease, there is no cure for HIV/AIDS. These drugs have reduced AIDS deaths in many developed nations, but HIV continues to decimate populations in Africa, Haiti, and parts of Asia. Therefore, effective methods and compositions for determining a prognosis for a subject infected with HIV, reducing a risk of an HIV infection, and treating or reducing a risk of developing AIDS are desirable.